POS1263 SMOKING INFLUENCE ON AUTOANTIBODY PROFILE AND DISEASE PROGRESSION IN SYSTEMIC SCLEROSIS: AN EUSTAR DATABASE ANALYSIS
Authors: J. Ciaffi, S. Liem, P. Wiland, T. Atsumi, G. Szücs, R. Pellerito, A. Balbir-Gurman, L. Czirják, E. Zanatta, I. Koetter, A. Shah, J. Henes, M. Matucci-Cerinic, P. Airò, F. Ursini, T. Huizinga, J. De Vries-Bouwstra
Journal: Annals of the Rheumatic Diseases (2023)

<h3>Background</h3> The available evidence suggests that there is no correlation between smoking and disease-specific cutaneous or pulmonary manifestations in systemic sclerosis (SSc) [1]. However, three studies showed that never-smokers had a higher prevalence of anti-topoisomerase I (ATA) positivity than ever-smokers [1-3], which might be important for risk stratification. <h3>Objectives</h3> This study has two objectives: (1) to determine whether patients exposed to cigarette smoking present a distinct autoantibody profile; (2) to determine whether smoking confers different risk of disease progression in men and women or in patients with different autoantibodies. <h3>Methods</h3> Adult patients registered in the EUSTAR database fulfilling the SSc classification criteria, whose information about smoking habit was available and consistent during follow-up, were included. Patients were categorised as "ever-smokers" or "never-smokers" at the first visit. Differences in autoantibody profile were analysed using Chi-square test. Kaplan-Meier curves and log-rank tests were performed to compare outcomes between ever-smokers and never-smokers for up to 20 years of follow-up. The association between smoking habit and progression in disease domains was estimated using Cox proportional hazards models adjusted for age, antibodies (anti-centromere – ACA, and ATA), sex and disease duration. Additionally, cox models including the interaction between smoking status and sex, and between smoking status and autoantibody positivity, were built to assess effect modification. The risk of death, newly diagnosed interstitial lung disease (ILD) and cardiac involvement were evauated. Furthermore, we investigated worsening of functional impairment in patients with ILD and progression of cutaneous involvement. The study protocol was reviewed and approved by the EUSTAR board (project number CP 126). <h3>Results</h3> At the time of data extraction (July 5, 2022), 12314 patients met the inclusion criteria. Of these, 84.4% were female and mean age was 55.5±13.8 years. ACA was positive in 38% of patients and ATA in 32%; 4271 individuals (35%) were ever-smokers. Among never-smokers, 35% of patients was ATA positive, compared to 27% among ever-smokers (p &lt;0.001). When stratifying for sex, this difference was accounted for by female patients: 34% of never-smoking females was ATA positive compared to 21% of ever-smoking women (p &lt;0.001). In men, no statistically significant difference in ATA positivity was observed. Survival was significantly lower in ever-smokers than in never-smokers (46% vs 55%; log-rank test p=0.0032; Figure 1). In multivariable Cox regression analysis, ever-smoking was associated with mortality (HR 1.24; 95% CI 1.07 to 1.43). Evidence for an interaction between smoking status and sex was found (HR of interaction term 1.44, 95% CI 1.03 to 2.03). Cox proportional hazards models did not show an increased risk of developing ILD (HR 1.03; 95% CI 0.92 to 1.16) or cardiac involvement (HR 1.10; 95% CI 0.99 to 1.21), neither of functional worsening in ILD (HR 1.01; 95% CI 0.93 to 1.10) or cutaneous progression (HR 1.11; 95% CI 0.97 to 1.26) for ever-smokers. <h3>Conclusion</h3> Our study in a large cohort of SSc patients from the EUSTAR registry confirms that ever-smoking is associated with lower prevalence of ATA positivity among female SSc patients. Our findings indicate that ever-smoking patients have a worse survival during follow-up, while no association between smoking and development of ILD, cardiac involvement or skin progression emerged. <h3>References</h3> [1]Jaeger VK et al. Smoking in Systemic Sclerosis: A Longitudinal European Scleroderma Trials and Research Group Study. Arthritis Rheumatol 2018. [2]Chaudhary P et al. Cigarette smoking is not a risk factor for systemic sclerosis. Arthritis Rheum 2011. [3]Ciaffi J et al. Smoking and systemic sclerosis: influence on microangiopathy and expression of anti-topoisomerase I antibodies in a monocentric cohort. Clin Exp Rheumatol 2020. <h3>Acknowledgements:</h3> NIL. <h3>Disclosure of Interests</h3> None Declared.